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Evaluation of insertion/deletion (I/D) polymorphisms of ACE gene and circulating levels of angiotensin II in congenital anomalies of the kidney and urinary tract

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Abstract

Background

Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II (Ang II) and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene and the circulating levels of Ang II are associated with any CAKUT phenotype or CAKUT in general.

Methods and results

Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association was detected between ACE I/D polymorphism and CAKUT and UPJO, VUR, and MCDK phenotypes. In a subset of 80 CAKUT patients and 80 controls, plasma levels of Ang II were measured. No significant differences were found between CAKUT patients and controls, even in regard to comparisons of UPJO, VUR and MCDK with control group.

Conclusion

Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms nor with differences in plasma levels of Ang II in this Brazilian pediatric population.

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Funding

This work was partially supported by Brazilian National Council of Research Development (CNPq—Grant # 302153/2019-5), Coordination of High Education Level Personnel (CAPES) and Foundation of Research of Minas Gerais (FAPEMIG).

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Authors and Affiliations

  1. Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2nd Floor, Room #281, Belo Horizonte, MG, Zip Code: 30130-100, Brazil

    Pedro Antunes Pousa, Tamires Sara Campos Mendonça, Larissa Marques Fonseca, André Rolim Belisário & Ana Cristina Simões e Silva

  2. Pediatric Nephrology Unit, Department of Pediatrics, Faculty of Medicine, UFMG, Belo Horizonte, Brazil

    Eduardo Araújo Oliveira & Ana Cristina Simões e Silva

Authors
  1. Pedro Antunes Pousa
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  2. Tamires Sara Campos Mendonça
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  3. Larissa Marques Fonseca
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  4. Eduardo Araújo Oliveira
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  5. André Rolim Belisário
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  6. Ana Cristina Simões e Silva
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Contributions

PAP, TSCM and LMF wrote the first draft. ARB performed laboratorial and statistical analyses. ACSS and ARB conceptualized the study, made general supervision and revised the manuscript. ACSS submitted the final version of the manuscript, which is approved by all authors.

Corresponding author

Correspondence to Ana Cristina Simões e Silva.

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This study was approved by the local Ethics Committee.

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All subjects involved in this study gave consent and assented to participate in this study.

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All subjects involved in this study gave consent and assented for publication.

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Pousa, P.A., Mendonça, T.S.C., Fonseca, L.M. et al. Evaluation of insertion/deletion (I/D) polymorphisms of ACE gene and circulating levels of angiotensin II in congenital anomalies of the kidney and urinary tract. Mol Biol Rep 49, 4341–4347 (2022). https://doi.org/10.1007/s11033-022-07269-5

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  • DOI: https://doi.org/10.1007/s11033-022-07269-5

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